Cocaine abusers often report difficulty abstaining from cocaine while intoxicated with alcohol, and alcoholism and cocaine dependence have strong comorbidity. Therefore, we sought to determine whether alcohol intoxication would increase cocaine-craving induced by exposure to videotapes of an individual self-administering cocaine compared to a control tape of an individual painting. Subjects were 12 male residential volunteers with histories of both heavy alcohol and cocaine use. They drank water the first day, and a high (1.1 g/kg), moderate (0.64 g/kg), placebo (0.0 g/kg) dose of alcohol, or water on 4 separate (approx. alternate) days in pseudo-randomized order in double-blind fashion. Continuous self-report of desire for cocaine and autonomic measures were recorded before drinking, and during and after watching the stimulus tapes in the rising and falling BAC curves. Although mean levels of cocaine-craving were not intense, subjects reported significantly more cocaine-craving after ingestion of alcohol; this effect was nonsignificantly greater in the rising BAC curve when BAC was highest. We then divided subjects into 7 who craved cocaine and 5 with minimal or no craving during the entire experiment; these two groups had equivalent cocaine and alcohol histories. High cocaine-cravers had trait characteristics of significantly lower resting heart rate, higher vagal tone index, and greater general motor activity on a stabilometer under their chairs both before and after drinking. Lower resting heart rates among high cocaine-cravers was replicated in a second (nonresidential) study with 20 cocaine abusers. The autonomic pattern for high cocaine-cravers parallels that of "fussy," irritable, dysregulated infants. The results suggest a role for alcohol intoxication in craving for cocaine. They also underscore the potential importance of individual differences in drug-craving among users with equivalent abuse histories.